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bioRxiv · 10.1101/2024.04.24.590896

A look beyond the QR code of SNARE proteins

Yadav, D.·Hacisuleyman, A.·Dergai, M.·Khalifeh, D.·Abriata, L. A.·Dal Peraro, M.·Fasshauer, D.
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Abstract

Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor (SNARE) proteins catalyze the fusion process of vesicles with target membranes in eukaryotic cells. To do this, they assemble in a zipper-like fashion into stable complexes between the membranes. Structural studies have shown that the complexes consist of four different helices, which we subdivide into Qa-, Qb-, Qc-, and R-helix on the basis of their sequence signatures. Using a combination of biochemistry, modeling and molecular dynamics, we investigated how the four different types are arranged in a complex. We found that there is a matching pattern in the core of the complex that dictates the position of the four fundamental SNARE types in the bundle, resulting in a QabcR complex. In the cell, several different cognate QabcR-SNARE complexes catalyze the different transport steps between the compartments of the endomembrane system. Each of these cognate QabcR complexes is compiled from a repertoire of about 20 SNARE subtypes. Our studies show that exchange within the four types is largely tolerated structurally, although some non-cognate exchanges lead to structural imbalances. This suggests that SNARE complexes have evolved for a catalytic mechanism, a mechanism that leaves little scope for selectivity beyond the QabcR rule.

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Yadav, D., Hacisuleyman, A., Dergai, M., Khalifeh, D., Abriata, L. A., Dal Peraro, M., Fasshauer, D.. 2024-04-24. A look beyond the QR code of SNARE proteins. https://doi.org/10.1101/2024.04.24.590896

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